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    Additively manufactured continuous processing reactor system for producing liquid-based pharmaceutical substances
    (Multidisciplinary Digital Publishing Institute (MDPI), 2024) Khabiyev, Alibek; Dilibal, Savaş; Mussulmanbekova, Assel; Kanapiya, Magzhan; Kerimkulov, Daniyar
    In this study, an AM-based continuous processing reactor system was designed, manufactured, and assembled on a laboratory scale for the generation of pharmaceutical substances with an improved process control. The developed AM-based (additively manufactured) continuous pharmaceutical reactor system for the synthesis of metronidazole derivatives aimed to optimize both the physical and the chemical processes with time savings. Using AM, we were able to build reactor subcomponents with complex designs and precise dimensions, which facilitated the precise control of the reaction parameters and reduced the amount of chemicals required compared to macroscale reactors. The assembly of the whole reactor system consisted of main reactor bodies, mixers, valves, heat exchangers, electrical motors, and a microcontroller system. The assembled reactor system revealed a continuous flow of reagents and ensured uniform mixing and reaction conditions, thereby increasing the process efficiency and product quality. Five metronidazole derivatives were synthesized via two continuous processes, involving metronidazole reduction and its subsequent reactions with terephthalic aldehyde and anthracen-9(10H)-one to form Schiff bases. The optimal conditions were determined as follows: compound A (72% yield, 120 min, 55 °C), compounds B and C (63% and 68% yield, respectively, 8 h, 65 °C), and compounds D and E (74% and 85% yield, respectively, 8 h, 45 °C).
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    Additively manufactured small-volume continuous manufacturing reactor system for C–C cross-coupling reactions
    (National Information and Documentation Centre, 2026) Khabiyev, Alibek; Savas, Dilibal; Assel, Mussulmanbekova; Rafikova Kh.S.; Kanapiya, Magzhan; Medet, Dyussembayev; Iskender, Aidana
    Continuous manufacturing (CM) is increasingly recognized as a transformative approach in pharmaceutical and chemical production, offering enhanced efficiency, reproducibility, and sustainability compared to conventional batch processing. This study presents the development and application of an additively manufactured PEEK-based small-volume continuous reactor system for the three-stage Suzuki–Miyaura synthesis of biphenyl. The process integrated ligand synthesis, catalyst precursor formation, and the cross-coupling reaction within modular reactors, achieving high product selectivity and reproducibility. Comparative analysis with traditional batch synthesis revealed superior performance for the continuous system, including faster kinetics, shorter residence times, improved yields (up to ~100% for catalyst C within 10 minutes at 100 °C), and reduced waste generation. Additive manufacturing enabled the rapid prototyping of reactors with optimized geometries featuring integrated mixing and heat exchange, ensuring precise control of flow rates and thermal conditions. Beyond pharmaceutical applications, the system demonstrated significant potential for hydrometallurgical processes such as leaching, solvent extraction, and electrochemical metal recovery, where continuous flow operation offers substantial advantages in efficiency and sustainability. These findings underscore the synergy of CM, additive manufacturing, and process analytical technology as a flexible and environmentally responsible platform. The developed reactor system provides a pathway for scalable, modular, and on-demand chemical manufacturing, with broad implications for both high-value drug synthesis and sustainable resource management.